Analysis of Hi-C data using SIP effectively identifies loops in organisms from C. elegans to mammals
Analysis of Hi-C data using SIP effectively identifies loops in organisms from C. elegans to mammals
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DOI：
10.1101/gr.257832.119
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发表时间：
2020-03-01
期刊：
影响因子：
7
通讯作者：
Corces, Victor G.
中科院分区：
文献类型：
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作者：
Rowley, M. Jordan;Poulet, Axel;Corces, Victor G.
染色质环是三维核组织的主要组成部分，在Hi-C图中视觉上明显表现为强烈的点对点相互作用。这些回路的识别是大多数Hi-C分析的关键部分。然而，目前的方法往往错过视觉上明显的CTCF环Hi-C数据集从哺乳动物，他们完全无法识别其他生物体中的高强度循环。我们提出SIP，显着的交互峰值调用者，和SIPMETA，这是平台独立的程序来识别和表征这些循环的时间和内存效率的方式。我们表明，SIP是抗噪声和测序深度，并可用于检测环，以前错过了人类细胞以及环在其他生物体。SIPMeta通过考虑曼哈顿距离来校正常见的可视化伪影，以创建Hi-C和HiChIP数据的平均图。然后，我们证明，使用SIP和SIPMeta可以通过表征几种转录因子对人类细胞中CTCF环稳定性的贡献来获得生物学见解。我们还注释环与SMC成分的剂量补偿复合物（DCC）在秀丽隐杆线虫，并证明环锚代表双向块对称循环挤出。这与不对称挤出形成对比，直到被CTCF单向阻断，这被认为发生在哺乳动物中。使用HiChIP和多路连接事件，我们发现DCC环形成了一个强相互作用的网络，可能有助于C中X染色体范围的缩合。秀丽的雌雄同体。
Chromatin loops are a major component of 3D nuclear organization, visually apparent as intense point-to-point interactions in Hi-C maps. Identification of these loops is a critical part of most Hi-C analyses. However, current methods often miss visually evident CTCF loops in Hi-C data sets from mammals, and they completely fail to identify high intensity loops in other organisms. We present SIP, Significant Interaction Peak caller, and SIPMeta, which are platform independent programs to identify and characterize these loops in a time- and memory-efficient manner. We show that SIP is resistant to noise and sequencing depth, and can be used to detect loops that were previously missed in human cells as well as loops in other organisms. SIPMeta corrects for a common visualization artifact by accounting for Manhattan distance to create average plots of Hi-C and HiChIP data. We then demonstrate that the use of SIP and SIPMeta can lead to biological insights by characterizing the contribution of several transcription factors to CTCF loop stability in human cells. We also annotate loops associated with the SMC component of the dosage compensation complex (DCC) in Caenorhabditis elegans and demonstrate that loop anchors represent bidirectional blocks for symmetrical loop extrusion. This is in contrast to the asymmetrical extrusion until unidirectional blockage by CTCF that is presumed to occur in mammals. Using HiChIP and multiway ligation events, we then show that DCC loops form a network of strong interactions that may contribute to X Chromosome-wide condensation in C. elegans hermaphrodites.